Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression
Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/11/1460 |
| _version_ | 1797761284506124288 |
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| author | Dong Uk Im Sang Chon Kim Gia Cac Chau Sung Hee Um |
| author_facet | Dong Uk Im Sang Chon Kim Gia Cac Chau Sung Hee Um |
| author_sort | Dong Uk Im |
| collection | DOAJ |
| description | Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity, remains unclear. Here, we show that carbamazepine increased the expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and fatty acid synthase (FASN) in 3T3-L1 cells. Notably, carbamazepine inhibited the expression levels of β-catenin, a negative regulator of adipogenesis, leading to enhanced adipogenesis. Conversely, β-catenin overexpression abolished the effect of carbamazepine on adipogenic gene expression. However, depletion of β-catenin further enhanced PPARγ expression. In addition, carbamazepine reduced β-catenin expression by lowering the levels of phospho-low density lipoprotein receptor-related protein 6 (p-LRP6) and phospho-glycogen synthase kinase 3β (p-GSK3β) in Wnt/β-catenin signaling. Moreover, carbamazepine reduced Wnt mRNA expression and decreased the promoter activities of TCF, the target of β-catenin during adipogenesis. These results suggest that carbamazepine enhances adipogenesis by suppressing Wnt/β-catenin expression, indicating its potential effects on obesity-related metabolism. |
| first_indexed | 2024-03-12T19:10:44Z |
| format | Article |
| id | doaj.art-0c58fd032c4f439193b34b11dd9f0441 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:10:44Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0c58fd032c4f439193b34b11dd9f04412023-08-02T05:52:10ZengMDPI AGCells2073-44092019-11-01811146010.3390/cells8111460cells8111460Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin ExpressionDong Uk Im0Sang Chon Kim1Gia Cac Chau2Sung Hee Um3Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, KoreaDepartment of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, KoreaDepartment of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, KoreaDepartment of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, KoreaCarbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity, remains unclear. Here, we show that carbamazepine increased the expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and fatty acid synthase (FASN) in 3T3-L1 cells. Notably, carbamazepine inhibited the expression levels of β-catenin, a negative regulator of adipogenesis, leading to enhanced adipogenesis. Conversely, β-catenin overexpression abolished the effect of carbamazepine on adipogenic gene expression. However, depletion of β-catenin further enhanced PPARγ expression. In addition, carbamazepine reduced β-catenin expression by lowering the levels of phospho-low density lipoprotein receptor-related protein 6 (p-LRP6) and phospho-glycogen synthase kinase 3β (p-GSK3β) in Wnt/β-catenin signaling. Moreover, carbamazepine reduced Wnt mRNA expression and decreased the promoter activities of TCF, the target of β-catenin during adipogenesis. These results suggest that carbamazepine enhances adipogenesis by suppressing Wnt/β-catenin expression, indicating its potential effects on obesity-related metabolism.https://www.mdpi.com/2073-4409/8/11/1460carbamazepineobesityadipocyte differentiationadipogenesiswnt/β-catenin |
| spellingShingle | Dong Uk Im Sang Chon Kim Gia Cac Chau Sung Hee Um Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression Cells carbamazepine obesity adipocyte differentiation adipogenesis wnt/β-catenin |
| title | Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression |
| title_full | Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression |
| title_fullStr | Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression |
| title_full_unstemmed | Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression |
| title_short | Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-Catenin Expression |
| title_sort | carbamazepine enhances adipogenesis by inhibiting wnt β catenin expression |
| topic | carbamazepine obesity adipocyte differentiation adipogenesis wnt/β-catenin |
| url | https://www.mdpi.com/2073-4409/8/11/1460 |
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